In recent years, post-genome research known as proteome has been actively pursued. Something that has attracted particular attention in this research is research that attempts to elucidate the three-dimensional structure of proteins; such research is called “structural genome science.” Elucidation of the structures and functions of proteins is an important research field in the life sciences, and is directly connected to the treatment of diseases and the creation of drugs; accordingly, the analysis of detailed steric structures is indispensable. X-ray crystal structure analysis may be cited as one important means of such analysis; in order to apply X-ray crystal structure analysis, it is necessary to crystallize the macromolecular substances that are the object of analysis.
In the growth of macromolecular crystals, as in the growth of inorganic crystals and organic low-molecular crystals, crystals having a shape that reflects the molecular structure and growth conditions are grown. Furthermore, since crystallization conditions and growth conditions for obtaining good-quality single crystals have not been established for most macromolecular substances, control of crystallization and subsequent growth control are extremely difficult. Accordingly, there have been problems in terms of crystal quality, and problems such as polycrystallization due to the mutual adhesion of crystals that are deposited in close proximity to each other have frequently been encountered.
For example, in cases where X-ray crystal structure analysis is to be performed, single crystals that have the desired shape and that show good quality are required. Accordingly, the crystals are generally obtained by optimizing crystallization and growth conditions. As was described above, however, it is extremely difficult to obtain such crystals for macromolecular substances. Accordingly, there are cases in which portions with the size and shape or good crystal quality required for X-ray crystal structure analysis are extracted from the crystals obtained, or in which working such as the cutting of single crystals from polycrystals is performed.
However, since macromolecular crystals are far softer and more brittle than (for example) inorganic substances or organic low-molecular substances, damage such as cracking and splitting occurs in peripheral parts if a large impact is applied during working. Furthermore, such crystals are also sensitive to temperature variations; it is known that such crystals readily are denatured if heat is applied.
Thus, since macromolecular crystals are extremely difficult to handle, it is extremely difficult to use working techniques that have become widespread in inorganic crystals and other materials “as is” in macromolecular crystals, so that reliable crystal working techniques have not yet been established.
Currently used working methods for macromolecular crystals are working methods using blades, needles, or the like that require mechanical contact with the crystal. In such methods, working is performed manually under observation by means of a microscope or the like; these methods are used mainly to cut macromolecular crystals.
However, macromolecular crystals are mechanically brittle compared to general crystals, so that when working is performed by means of a blade or needle, there is a possibility that the cut surface will crumble as a result of the shear forces to which the cut surface is subjected. Accordingly, currently used macromolecular crystal working methods are methods in which many elements are left to chance, and the probability of success and reproducibility are low even in cases where working is performed by a person with professional skill. In the case of such methods, furthermore, although relatively simple working such as the cutting of crystals is possible, application is extremely difficult in cases where complicated and precise working is required.